Motor signs during the course of Alzheimer disease.
Scarmeas N, Hadjigeorgiou GM, Papadimitriou A, Dubois B, et al.;
Commented by , 24 Jan 2005
Aim of the study
To describe the progression and identify predictors of individual motor signs (MOSIs) in Alzheimer’s disease (AD).
Method
Cohort study of 474 patients with AD at different stages followed semi annually for up to 13.1 years (mean 3.6 years) in five centres in Europe and the United States. MOSIs were rated using a standardized section of the United Parkinson’s Disease Rating Scale (UPDRS).
Results
An average of 6.4 assessments were made per patient. At least one MOSI was detected in 13% of patients at first examination and in 36% at last examination. Total MOSI score increased at an annual rate of 3% of the total possible score. Rates of annual changes were similar for speech/facial expression, rigidity, posture/gait, bradykinesia, with an occurrence increasing from 3 to 6% at first assessment up to 22 to 29% at last assessment. Tremor was less frequent throughout the course of disease (4% at first, 7% at last visit).
Professor Gauthier's comments
MOSIs are important in AD because their very early appearance could suggest alternative diagnosis such as subcortical ischemic vascular dementia, Dementia with Lewy Bodies (DLB) or hydrocephalus. In probable AD their emergence over time predict cognitive decline, need for institutionalisation and death.
The UPDRS has been used in clinical trials for AD in moderate to severe stages such as donepezil vs. placebo (ref. 1) and failed to detect a worsening in MOSI from the use of donepezil. In a recent study for Parkinson’s Dementia comparing rivastigmine to placebo (ref. 2), although there was a significant increase in resting tremor associated with rivastigmine, the UPDRS total score did not change, nor did the tremor-related items, suggesting that this increase in tremor was not clinically significant.
Examination for MOSIs is important to detect extrapyramidal side effects from neuroleptics, which can cause clinically significant increase in rigidity and bradykinesia, even in low doses. The worse case scenario is in patients with DLB where neuroleptic hypersensitivity can lead to death.
The look for MOSIs should thus be part of routine clinical practice in assessing patients with dementia of any type, possibly using a short version of the UPDRS including the most relevant items (speech/facial expression, rigidity, posture/gait, bradykinesia), as described in this article.
References
1. Feldman et al. A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease. Neurology 2001; 57 (4); 613-620
2. Emre et al. Rivastigmine for dementia associated with Parkinson's Disease . New England Journal of Medicine 2004; 351 (24); 2509-2518 (see also Professor Emre's article on CNSforum on this study)